Stanniocalcin-1 is a glycoprotein, a homologue of a hormone stanniocalcin, first discovered in bony fishes. In humans it is encoded by the STC1 gene. [5] [6]
This gene encodes a secreted, homodimeric glycoprotein that is expressed in a wide variety of tissues and may have autocrine or paracrine functions. The only known molecular function of human Stanniocalcin-1 to date is a SUMO E3 ubiquitin ligase activity in the SUMOylation cycle. However, STC1 interacts with many proteins in the cytoplasm, mitochondria, endoplasmatic reticulum, and in dot-like fashion in the cell nucleus. The N-terminal region of STC1 is the function region which is responsible to establish the interaction with its partners, including SUMO1. [7] Low-resolution studies shows that STC1 is an anti-parallel homodimer in solution and the cysteine 202 is responsible for its dimerization. All the 5 disulfide bonds of human STC1 are conserved and have the same profile of fish STC. [8] The gene contains a 5' UTR rich in CAG trinucleotide repeats. The encoded protein contains 11 conserved cysteine residues and is phosphorylated by protein kinase C exclusively on its serine residues.
The protein may play a role in the regulation of renal and intestinal calcium and phosphate transport, cell metabolism, or cellular calcium/phosphate homeostasis. Overexpression of human stanniocalcin 1 in mice produces high serum phosphate levels, dwarfism, and increased metabolic rate. This gene has altered expression in hepatocellular, ovarian, and breast cancers, [6] and is a putative molecular biomarker of leukemic microenvironment.
Proglucagon is a protein that is cleaved from preproglucagon. Preproglucagon in humans is encoded by the GCG gene.
The follicle-stimulating hormone receptor or FSH receptor (FSHR) is a transmembrane receptor that interacts with the follicle-stimulating hormone (FSH) and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning of FSH. FSHRs are found in the ovary, testis, and uterus.
The luteinizing hormone/choriogonadotropin receptor (LHCGR), also lutropin/choriogonadotropin receptor (LCGR) or luteinizing hormone receptor (LHR) is a transmembrane receptor found predominantly in the ovary and testis, but also many extragonadal organs such as the uterus and breasts. The receptor interacts with both luteinizing hormone (LH) and chorionic gonadotropins and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning during reproduction.
The constitutive androstane receptor (CAR) also known as nuclear receptor subfamily 1, group I, member 3 is a protein that in humans is encoded by the NR1I3 gene. CAR is a member of the nuclear receptor superfamily and along with pregnane X receptor (PXR) functions as a sensor of endobiotic and xenobiotic substances. In response, expression of proteins responsible for the metabolism and excretion of these substances is upregulated. Hence, CAR and PXR play a major role in the detoxification of foreign substances such as drugs.
Thyrotropin-releasing hormone receptor (TRHR) is a G protein-coupled receptor which binds thyrotropin-releasing hormone.
The gastric inhibitory polypeptide receptor (GIP-R), also known as the glucose-dependent insulinotropic polypeptide receptor, is a protein that in humans is encoded by the GIPR gene. GIP-R is a member of the 7-transmembrane protein family, a class of G protein coupled receptors. GIP-R is found on beta-cells in the pancreas where it serves as the receptor for the hormone Gastric inhibitory polypeptide (GIP).
The liver receptor homolog-1 (LRH-1) also known as NR5A2 is a protein that in humans is encoded by the NR5A2 gene. LRH-1 is a member of the nuclear receptor family of intracellular transcription factors.
The small heterodimer partner (SHP) also known as NR0B2 is a protein that in humans is encoded by the NR0B2 gene. SHP is a member of the nuclear receptor family of intracellular transcription factors. SHP is unusual for a nuclear receptor in that it lacks a DNA binding domain. Therefore, it is technically neither a transcription factor nor nuclear receptor but nevertheless it is still classified as such due to relatively high sequence homology with other nuclear receptor family members.
V-erbA-related protein 2 (EAR-2) also known as NR2F6 is a protein that in humans is encoded by the NR2F6 gene. V-erbA-related protein 2 is a member of the nuclear receptor family of intracellular transcription factors. It is named after its similarity to v-erbA, a helper of an oncoprotein called v-erbB in avian erythroblastosis virus.
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Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene.
Estrogen-related receptor alpha (ERRα), also known as NR3B1, is a nuclear receptor that in humans is encoded by the ESRRA gene. ERRα was originally cloned by DNA sequence homology to the estrogen receptor alpha, but subsequent ligand binding and reporter-gene transfection experiments demonstrated that estrogens did not regulate ERRα. Currently, ERRα is considered an orphan nuclear receptor.
Thyroid hormone receptor alpha (TR-alpha) also known as nuclear receptor subfamily 1, group A, member 1 (NR1A1), is a nuclear receptor protein that in humans is encoded by the THRA gene.
Corticotropin-releasing hormone receptor 2 (CRHR2) is a protein, also known by the IUPHAR-recommended name CRF2, that is encoded by the CRHR2 gene and occurs on the surfaces of some mammalian cells. CRF2 receptors are type 2 G protein-coupled receptors for corticotropin-releasing hormone (CRH) that are resident in the plasma membranes of hormone-sensitive cells. CRH, a peptide of 41 amino acids synthesized in the hypothalamus, is the principal neuroregulator of the hypothalamic-pituitary-adrenal axis, signaling via guanine nucleotide-binding proteins (G proteins) and downstream effectors such as adenylate cyclase. The CRF2 receptor is a multi-pass membrane protein with a transmembrane domain composed of seven helices arranged in a V-shape. CRF2 receptors are activated by two structurally similar peptides, urocortin II, and urocortin III, as well as CRH.
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Stanniocalcin-2 is a protein that in humans is encoded by the STC2 gene.
Thyroid receptor-interacting protein 11 is a protein that in humans is encoded by the TRIP11 gene.
High mobility group nucleosome-binding domain-containing protein 3 is a protein that in humans is encoded by the HMGN3 gene.
Stanniocalcin is a family of hormones which regulate calcium and phosphate balance in the body. The first stanniocalcin discovered was from fish and was identified as the principal calcium-reducing (hypocalcaemic) factor. It was isolated from special organs in fish called corpuscles of Stannius, hence the name stanniocalcin. Chemically, stanniocalcins are glycosylated proteins having a molecular mass of 50 kDa. They exist in molecular pairs (homodimers) and are joined together by disulfide linkage. Stanniocalcins are made up of approximately 250 amino acids.
The corpuscles of Stannius are special endocrine organs in the kidney in fish and are responsible for maintaining calcium balance. They are found only in bony fishes. They were discovered and described by a German anatomist Hermann Friedrich Stannius in 1839. Stannius considered them as functionally similar to adrenal glands in mammals. But they have later been found to be anatomically different as they are derived from different tissues of the embryo. Structurally the corpuscles are a large number of spherical bodies separated from each other by loose connective tissues. Each body or lobule is in turn composed of several columnar cells, which contain secretory granules and are, thus, secretory in function. Each Secretory granule is spherical in shape and measures 0.5 to 1 μm in diameter. Their possible endocrine nature, i.e. producing hormone, was suspected from the complete anatomical description, and it was believed to be responsible for regulating calcium level in the blood. The hormone was identified as stanniocalcin.